The aim of this study was to examine the effect of root of C. colocynthis on the biochemical parameters of normal and alloxan-induced diabetic rats. Diabetes mellitus was induced by intraperitoneal (120 mg/kg b.w.) injection of alloxan monohydrate for three days and the animals showing blood glucose level in the range of 175-300 mg/dL were selected for study. The blood glucose concentrations of the animals were measured at the beginning of the study and the measurements were repeated on 3rd, 5th and 7th day after the start of the experiment. On day 7, blood was collected by cardiac puncture under mild ether anesthesia. Aqueous extract of roots of Citrullus colocynthis showed significant reduction in blood sugar level (58.70%) when compared with chloroform (34.72%) and ethanol extracts (36.60%) (p < 0.01). The aqueous extracts showed improvement in parameters like body weight, serum creatinine, serum urea and serum protein as well as lipid profile and also restored the serum level of bilirubin total, conjugated bilirubin, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transminase (SGPT) and alkaline phosphatase (ALP).