Abstract: In order to study the effects of cadmium exposure on antioxidant and nonspecific immune system of Megalobrama amblycephala, fish were subjected to cadmium concentrations of 0 (control group), 0.05, 0.10, and 0.50 mg/L cadmium for 60d. Results indicated an enlargement of the gall bladder proportional to cadmium concentration, with the gall bladder turning dark green at 0.50 mg/L cadmium exposure. Liver and spleen body indices were significantly elevated in all cadmium-exposed groups compared to the control group, with spleen body index rising progressively with cadmium concentration. The highest concentration of cadmium was in the gut (240±1.41) mg/kg, followed by middle kidney (190±2.12) mg/kg, liver (57±1.35) mg/kg, gill (47±1.54) mg/kg, spleen (16±0.27) mg/kg, head kidney (14±0.37) mg/kg, heart (11±0.36) mg/kg, sperm (2.8±0.42) mg/kg, ovary (1.2±0.21) mg/kg, brain (0.65±0.12) mg/kg, and muscle had the lowest Cd content (0.35±0.04) mg/kg after 0.50 mg/L cadmium exposure culture for 60 days. Fish exposed to this concentration exhibited a yellowish body color, spleen swelling with vacuolated cells, blackened liver with bleeding, enlarged liver sinuses, and chaotic structure. Intestinal villi were shorter with thickened muscle layer, while gill lamellae displayed aneurysms, cell proliferation. and curvature. Serum levels of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) decreased gradually with increasing cadmium concentration, while lysozyme (Lys) content and activities of alkaline phosphatase (AKP), acid phosphatase (ACP), and catalase (CAT) initially increased and then decreased. High cadmium exposure group (0.50 mg/L) significantly reduced Lys content, AKP, and ACP activities compared to the control group. The mRNA expression levels of il-6, il-1β, il-10, tnf-ɑ and c3 genes in head kidney, spleen, and liver decreased with rising cadmium concentration, while tnf-ɑ, c3, and igm gene expression in the intestine, and c3 genes expression in the gill increased. Expression of the igm gene in head kidney significantly increased at low cadmium concentrations but decreased at high concentrations. The results demonstrated that low cadmium levels induced toxic excitability in Megalobrama amblycephala, but higher concentrations damaged immune tissue and inhibited the immune system. Cadmium exerts toxic on both the antioxidant and the immune system of Megalobrama amblycephala, providing a basic experimental data for further exploring the toxic mechanism of cadmium on fish.