The present study evaluates the prophylactic role of Ananas comosus ethanolic extract (ACEE) against sodium oxalate (NaOx) - induced nephrolithiasis. Forty two rats were allocated into the following set of groups (6 rats/set group). Normal rats divided to two groups, one of them received distilled water (Control group) and the other received ACEE (1000 mg/kg body weight, p.o) for 7 consecutive days. Urolithiatic rat groups which divided into five subgroups injected with sodium oxalate (70 mg NaOx /kg body weight, i.p) for 7 days; and concurrently received oral administration of distilled water (Urolithiatic group, Vehicle), ACEE and Cystone. Interestingly, ACEE showed a beneficial effect in preventing stone formation. Significant reductions were obtained in the urinary and serum calcium and phosphate excretion along with an increase in magnesium excretion in urolithiatic rats treated with ACEE. Urolithiatic rats treated with ACEE and cystone significantly increased the urinary volume. Administration of ACEE caused significant amelioration in renal function which suggests antilithiatic activity of ACEE. Moreover, urolithiatic rats treated with ACEE significantly attenuated oxidative damage induced by NaOx. In conclusion, ACEE has antilithiatic efficacy may be due to its diuretic activity, antioxidant activity, beside its bioactive constituents which affecting calcium oxalate crystallization.