Modulation of metformin transporters could affect its pharmacokinetics/pharmacodynamics. The effects of naringenin on the renal tubular Organic Cation Transporter 1 (OCT1) and 2 (OCT2) protein expressions and subsequently the metformin clearance in diabetic rats are hereby investigated. Male Sprague Dawley rats were divided into 7 groups. Animals were daily treated orally with metformin (250 mg/kg) or naringenin (60 mg/kg) alone or both for 56 days. Blood glucose tests were done. Serum, urine, and kidney samples were collected. Naringenin alone or in combination with metformin significantly increased creatinine clearance and lowered plasma metformin concentrations in diabetic rats compared to controls. OCT1 and OCT2 protein expressions in renal tissues were unchanged in diabetic rats treated with either naringenin or metformin, respectively. However, co-administration of metformin and naringenin upregulated OCT2 expression in diabetic rats. Naringenin may stimulate renal uptake/excretion of metformin by increasing OCT2 protein expression which facilitates metformin clearance in diabetic rats.