Hi, the primary significance of it was that many native Americans and many settlers lost their lives through all the bloodshed.  A cycle of violence was started which was hard to stop.

Here's additional input from wikipedia:

The Sand Creek Massacre resulted in a heavy loss of life and material possessions by the Cheyenne and Arapaho bands affected by the massacre. It also devastated the Cheyenne's traditional government, due to the deaths at Sand Creek of eight of 44 members of the Council of Forty-Four, including White Antelope, One Eye, Yellow Wolf, Big Man, Bear Man, War Bonnet, Spotted Crow, and Bear Robe, as well as headmen of some of the Cheyenne's military societies.^[17] Among the chiefs killed were most of those who had advocated peace with white settlers and the U.S. government.^[18] The effect of this on Cheyenne society was to exacerbate the social and political rift between the traditional council chiefs and their followers on the one hand and the militaristic Dog Soldiers on the other.

Beginning in the 1830s, the Dog Soldiers had evolved from the Cheyenne military society by that name into a separate, composite band of Cheyenne and Lakota warriors that took as its territory the headwaters country of the Republican and Smoky Hill rivers in southern Nebraska, northern Kansas, and the northeast of Colorado Territory. By the 1860s, as conflict between Indians and encroaching whites intensified, the influence wielded by the militaristic Dog Soldiers, together with that of the military societies within other Cheyenne bands, had become a significant counter to the influence of the traditional Council of Forty-Four chiefs, who were more likely to favor peace with the whites.^[19] To the Dog Soldiers, the Sand Creek Massacre illustrated the folly of the peace chiefs' policy of accommodating the whites through the signing of treaties such as the first Treaty of Fort Laramie and the Treaty of Fort Wise^[2] and vindicated the Dog Soldiers' own militant posture towards the whites.^[19]

The traditional Cheyenne clan system was dealt a fatal blow by the events at Sand Creek. It had already been dealt a severe blow by an 1849 cholera epidemic which killed perhaps half the Southern Cheyenne population^[20], especially the Masikota and Oktoguna bands,^[21] and further weakened by the emergence of a separate Dog Soldiers band.^[22] Hardest hit by the massacre were the Wutapai (Black Kettle's band), perhaps half of the Hevhaitaniu including the clan's chiefs Yellow Wolf and Big Man, about half of the Oivimana under War Bonnet, and heavy losses to the Hisiometanio (Ridge Men) under White Antelope. Chief One Eye was also killed along with many of his band. The Suhtai clan and the Heviqxnipahis clan under Chief Sand Hill experienced relatively few losses. The Dog Soldiers and the Masikota, who by that time had joined the Dog Soldiers, were not present at Sand Creek.^[23] Of about ten lodges of Arapahos under Chief Left Hand, representing about fifty or sixty people, only a handful escaped with their lives.^[24

Revenge

After this event, many Cheyenne, including the great warrior Roman Nose, and Arapaho men joined the Dog Soldiers and sought revenge on settlers throughout the Platte valley, killing as many as 200 civilians.