Objective: To investigate the potential activity of protocatechuic acid in female Wistar rats with letrozole-induced polycystic ovary syndrome (PCOS).Methods: Thirty rats were divided into five groups of six each. Group 1 received 0.5％ carboxy methyl cellulose orally and served as the normal control group; group 2 was treated orally with 1 mg/kg of letrozole daily for 21 days and served as the PCOS induced group; group 3 was orally administered with letrozole of 1 mg/kg for 21 days and further administered with standard drug of clomiphene citrate at a dose of 1 mg/kg body weight in 0.5％ carboxy methyl cellulose per oral and served as the standard group; groups 4 and 5 were administered with letrozole of 1 mg/kg for 21 days and further treated with protocatechuic acid orally at low dose of 5 mg/kg body weight and high dose of 15 mg/kg body weight respectively for 15 days. At the end of the study period, rats were subjected for the estimation of invasive blood pressure and heart rate, biochemical estimations and antioxidant assay. In addition, ovarian histomorphology was examined. Results: The PCOS was confirmed in the letrozole induced rats with increased concentration of androgen, abnormal lipid levels, glucose, glycosylated haemoglobin and also depletion of antioxidants. After protocatechuic acid treatment, the increased levels of testosterone due to induction of PCOS were restored to normal levels. Additionally, there was a consistent decrease in luteinizing hormone and follicle stimulating hormone levels in the treatment groups, followed by decrease in the number of cysts after treatment with protocatechuic acid. Histopathological observations showed a remarkable recovery of the ovarian tissue and the presence of normalized structure of antral follicle. Protocatechuic acid treatment restored all the parameters to normalcy and abolished cysts formation in ovaries of female rats. Conclusions: Protocatechuic acid shows potential protective effects in letrozole-induced PCOS rats. The protective effect is comparable to that of clomiphene citrate and thus shows its potential in the treatment of PCOS.