Toxicodenanes A-C (1-3), representing sesquiterpenoids with three new carbon skeletons, were isolated from the dried resin of Toxicodendron vernicifluum. Their structures were identified by spectroscopic data and X-ray diffraction crystallography. Their plausible biosynthetic route was proposed via the isolated intermediate (4). Compounds 2 and 3 could significantly inhibit overproduction of fibronectin, collagen IV, and IL-6 in high-glucose-induced mesangial cells in a dose- and time-dependent manner, showing their potential in diabetic nephropathy.