Introduction: Rising levels of plasma creatinine in the setting of acute unilateral ureteral obstruction (AUUO) often reflects acute renal failure, mandating kidney drainage. We hypothesize that reabsorption of peri-renal urine extravasation (PUE), a common result of UUO, contributes significantly to the elevation in plasma creatinine, rendering the latter an inaccurate benchmark for renal function. We explored this hypothesis in a rat model of AUUO and PUE.Methods: In total, 20 rats were equally divided into 4 groups. Groups 1 and 2 underwent unilateral ligation of the ureter with infiltration of rat’s urine (index group) or saline (control) into the peri-renal space. Two additional control groups underwent perirenal injection of either urine or saline without AUUO. Plasma creatinine levels were determined immediately prior to the procedure (T0), and hourly for 3 hours (T1, T2 and T3). Renal histology was investigated after 3 hours.Results: Rats in the index group had a significantly greater increase in plasma creatinine levels over 3 hours compared to all other groups (p < 0.05). At T3, average plasma creatinine levels for the index group increased by 96% (0.49 ± 0.18 mg/dL) compared to 46% (0.23 ± 0.06 mg/dL increase) in the AUUO and saline group, and less than 15% rise in both the non-obstructed control groups. Our study limitations includes lack of spontaneous PUE and intraperitoneal surgical approach.Conclusions: Absorption of peri-renal urine in the presence of AUUO is a significant contributor to rising plasma creatinine levels, beyond those attributable to the obstruction alone, and may overestimate the extent of the true renal functional impairment.