Objective To investigate the effects of different components of short-chain fatty acids (SCFAs) on depression-like behaviors and intestinal flora in chronic unpredictable mild stress (CUMS)-induced depressive rats. Methods Seventy-six healthy male rats were randomly divided into six groups. Rats in the acetate group (n=12),propionate group (n=15) and butyrate group (n=14) were given intraperitoneal injection (i.p.) of 50 mg/kg sodium acetate,100 mg/kg sodium propionate and 50 mg/kg sodium butyrate,respectively. Rats in the SCFAs group (n=12) were given i.p of 1∶1∶1 sodium acetate,sodium propionate and sodium butyrate mixed solution. Rats in the CUMS group (n=13) were given i.p of 1 mL/100 g saline. Rats in the control group (n=10) did not receive any treatment. Besides the control group,other groups were subjected to CUMS and intraperitoneal injection before stress for 28 days. The depression-like behaviors were assessed by sucrose preference test,forced swimming test,open field test,and then cecal fecal samples were collected to examine the composition of intestinal flora by 16S rRNA sequencing. Results Compared with the control group,the body weight of rats and the sugar preference coefficient decreased and the immobility time increased in the CUMS group (P<0.05). The butyrate group reversed the alterations in change of the sugar preference coefficient and the immobility time (P<0.05). Additionally,the sugar preference coefficient was elevated in the SCFAs group (P<0.05). The community structure of intestinal flora was changed in the CUMS group compared to the control group and was partially improved in the acetate group. The number of unique species reduced in the CUMS group but increased in the acetate group,propionate group,butyrate group and SCFAs group. LEfSe found the enrichment of Bifidobacterium in the propionate group and the enrichment of Collinsella in the SCFAs group. Conclusions Sodium butyrate significantly improves depressive-like behaviors of the CUMS-induced rats. Sodium acetate,sodium propionate,and short-chain fatty acid mixture can influence the composition of intestinal flora. However,their antidepressant effect is not significant. Sodium butyrate may be a better alternative for supplementing short-chain fatty acids in depression.