The aim of the study was to investigate the influence of chitosan oligosaccharide (COS) on some antioxidant and cytokine levels in the rat hippocampus as well as synaptophysin (SYP) immunoreactivity in the cerebral cortex of the cadmium (Cd) exposed rats. Thirty-two male albino Wistar rats were divided randomly into four equal groups as control (C; n = 8), Cd (n = 8), COS (n = 8), and Cd + COS (CdCOS; n = 8). The rats in the Cd and CdCOS groups received Cd chloride (CdCl2) (2 mg/kg/d) orally by gastric gavage three times a week for 4 weeks. Besides, COS (200 mg/kg/d) was administered to COS and CdCOS groups five times a week for 4 weeks. Then, they were decapitated and hippocampal/cerebral cortex tissue samples were taken for measurement of GSH levels, CAT and SOD activities, MDA values, TNF-α, IL-6, and IL-10 levels as well as SYP immunoreactivity. Although tissue GSH levels were determined the lowest in the Cd group, these values were attenuated with COS treatment in the CdCOS group (p <.01). In addition, TNF-α levels were alleviated by COS treatment in the CdCOS group when compared to Cd (p <.01). SYP-positive cells were investigated in the cerebral cortex and found mild in the CdCOS group. COS exhibits potential protective effects on Cd-induced neurotoxicity in rats.