Role and mechanism of renal PDI in blood pressure (BP) regulation has not been tested before. Here, we are testing this possibility in Sprague-Dawley (SD) rats. Rats were treated with PDI inhibitor bacitracin (100mg/kg, i.p./day for 14 days) followed by determining BP and renal AT1 receptor (AT1R) function in anesthetized rats. Renal AT1R function was determined as the ability of candesartan (an AT1R blocker) to increase diuresis and natriuresis. Second set of vehicle and bacitracin treated rats were used to determine biochemical parameters. Systolic BP increased in bacitracin-treated compared to vehicle-treated rats. Compared to vehicle, bacitracin-treated rats showed increased diuresis and natriuresis in response to candesartan, suggesting higher AT1R function in these rats. These were associated with higher renin activities in the plasma and renal tissues. Furthermore, urinary 8-isoprostane and kidney injury molecule-1 levels were higher whereas urinary antioxidant capacity was lower in bacitracin-treated rats. Renal protein carbonyl and nitrotyrosine levels also were higher in bacitracin compared to vehicle treated rats, suggesting oxidative stress burden in bacitracin-treated rats. Moreover, PDI activity decreased while its protein levels increased in renal tissues of bacitracin-treated rats. Also, nuclear levels of Nrf2 transcription factor, which regulates redox homeostasis, were decreased in bacitracin-treated rats. Further, tissue levels of Keap1, an Nrf2 inhibitory molecule, and tyrosine 216 phosphorylated GSK3β protein (GSK3β-pY216), an Nrf2 nuclear export protein, were increased in bacitracin treated rats. These results suggest that renal PDI by regulating keap1/Nrf2 pathway acts as an antioxidant, maintaining redox balance, renal AT1R function and BP in rats.