The aim of this study was to measure the effects of the aqueous extract of leaves of Adansonia digitata (AAD) in vitro on calcium oxalate (CaOx) nucleation and aggregation [by spectrophotometric time course measurements of optical density at 620 nm (OD620)]. For measuring calcium oxalate crystallization inhibitor activity agar gel model, and in vivo on experimentally induced CaOx urolithiasis in male Wistar rats. CaOx urolithiasis in rats was induced by intraperitoneal (i.p.) injection of sodium oxalate (NaOx) (7 mg/100 g/day for 7 days). AAD was administered orally (200 mg/kg/day for 7 days). Urine volume, pH, body weight, kidney weight (wet and dry), serum and urine level of creatinine, urea, magnesium (Mg2+), calcium (Ca2+) were evaluated on day 7. In addition, histopathological changes in kidney and oxalate in urine and kidney were evaluated. The results revealed that AAD inhibited the rate of crystal nucleation (SN) and aggregation (SA) and showed inhibitory activity on CaOx crystallization. The histopathological examination of kidneys revealed that AAD significantly reduced the incidence of CaOx crystal deposition. In addition, AAD significantly increased urinary excretion of Mg2+ along with a decrease of oxalate excretion. In conclusion, the aqueous extract contains potent antiurolithiatic substances which warrant further evaluation.