Objective: To study the effect of depression on renal function as well as oxidative stress and inflammatory response in patients with diabetic nephropathy. Methods: Patients with type 2 diabetes alone, patients with diabetic nephropathy and patients with diabetic nephropathy and depression treated in our hospital between May 2014 and September 2016 were selected as the research subjects and included in simple diabetes group, diabetic nephropathy group and complicated depression group, and the renal function indexes, oxidative stress indexes and inflammatory response indexes were detected. Results: Scr, BUN, CysC, ROS, MDA, 8-OHdG, IL-6, IL-18, MCP-1, ICAM-1, and TNF-α levels in serum as well as MA and A1M levels in urine of complicated depression group and diabetic nephropathy group were significantly higher than those of simple diabetes group while serum Mn-SOD, CAT, GSH-Px and T-AOC levels were significantly lower than those of simple diabetes group; Scr, BUN, CysC, ROS, MDA, 8-OHdG, IL-6, IL-18, MCP-1, ICAM-1, and TNF-α levels in serum as well as MA and A1M levels in urine of complicated depression group were significantly higher than those of diabetic nephropathy group while serum Mn-SOD, CAT, GSH-Px and T-AOC levels were significantly lower than those of diabetic nephropathy group. HAMD score was positively correlated with Scr, BUN, CysC, ROS, MDA, 8-OHdG, IL-6, IL-18, MCP-1, ICAM-1 and TNF-α levels in serum as well as MA and A1M levels in urine, and negatively correlated with Mn-SOD, CAT, GSH-Px and T-AOC levels in serum. Conclusion: Depression in patients with diabetic nephropathy can aggravate the renal injury and increase oxidative stress and inflammatory response.