The aim of the study was to investigate the effects of chitosan oligosaccharide (COS) treatment on oxidative stress and its relation with intestinal microflora in rats exposed to chronic cadmium toxicity. Animals were randomly divided into four groups as control (C; n=8), cadmium (Cd; n=8), chitosan oligosaccharide (COS; n=8), cadmium+chitosan oligosaccharide (Cd+COS; n = 8). After, cadmium chloride (CdCl2) (2mg /kg/ day) was orally administered to Cd and Cd+COS groups three times a week for 4 weeks. Chitosan oligosaccharide (200 mg/kg/day) was also orally administered to COS and Cd+COS groups five times a week for 4 weeks. After completion of the experiment, serum TAS, TOS levels, plasma ALT, AST, GGT, T.pro, Alb, Bil, Creat and BUN values were measured. Enterobacteriaceae, Lactococcus spp. and Lactobacillus spp. counts were also detected. Serum TOS values were detected extremely higher in Cd group animals when compared COS group (p <0,05). In the small intestine of the Cd group animals, Cd administration caused a 0.66 log decrease in the Lactococcus spp. count. In conclusion, it was found that the antimicrobial effect of both compounds decreased as a result of COS-Cd chelating in Cd + COS group.