Serum glucose, serum protein, serum glutamic oxalacetic transminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and hepatic and renal gluconeogenic enzymes [pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), fructose‐1,6‐diphosphatase (F‐1, 6‐DPase), and glucose‐6‐phosphatose (G‐6‐Pase)] were determined in rats treated daily with cadmium alone (0.25 mg/kg·d, injected ip) and in rats pretreated with spironolactone (50 mg/kg·d and 100 mg/kg·d, injected sc) prior to cadmium administration. Rats receiving no treatment, propylene glycol, or spironolactone (100 mg/kg·d, injected sc) were used as controls. The daily treatments were continued for an extended period of 90 d, and the rats were sacrificed at 30‐, 60‐, and 90‐d intervals during the continuous daily treatment schedule. Cadmium treatment significantly increased the amount of serum protein, glucose, serum enzymes, and all the four key gluconeogenic enzymes as compared to controls. Pretreatment of rats with spironolactone 6 h prior to cadmium injection daily antagonized the cadmium effect of the above parameters. It appears from these results that spironolactone reduces the effects of cadmium on the key gluconeogenic enzymes in rat kidney and liver.