Background: Crush syndrome or what is also known as traumatic rhabdomyolysis, is the leading cause of death following extrication from structural collapse due to earthquakes. Rhabdomyolysis is one of the most common reasons for acute kidney injury (AKI). The present study was designed to investigate the potential curative effect of wheat grass (WG) in acute kidney injury induced by glycerol (rat model of crush syndrome).Methods: Following a 24-hour period of water deprivation, male rats were randomly divided into 4 groups (6 rats each): The first group received an intramuscular (IM) injection of an equivalent volume of 0.9% saline into the hind limbs in divided dosages. The second group received IM injection of a single dose of 50% v/v glycerol in 0.9% saline (10 mL/kg), in equally divided doses to both hind limbs. The third group was injected a single dose of 50% v/v glycerol in 0.9% saline (10 mL/kg), into the hind limbs in divided dosages; then, the animals were administered WG (75 mg/kg, p.o.) twice per day for 3 successive days. The fourth group received only WG (75 mg/kg, p.o.) twice per day for 3 successive days. At the end of the experiments, animals were sacrificed; blood and kidneys were collected. Interleukin-6 (IL-6), interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), glutathione S-transferase (GST), and catalase (CAT) were measured using enzyme linked immunosorbent assay (ELISA). Superoxide dismutase (SOD), serum creatinine (SCr), blood urea nitrogen (BUN), and creatine kinase (CK) were estimated using assay kits. Nuclear factor kappa B (NF -KB) was measured using immunohistochemical analysis. Using thiobarbituric acid reactive substances (TBARS), the renal level of malondialdehyde (MDA) was determined. Histopathological examination was also performed.Results: The levels of BUN, SCr, the rhabdomyolysis marker CK, the oxidative damage marker MDA, and the inflammatory markers IL-6, IL-18, and NF -KB as well as the tubular injury markers KIM-1 and NGAL are increased in glycerol administration group. All these markers were significantly attenuated in those animals when treated with WG. Also, treatment with WG significantly improved GST, SOD, and CAT activities in glycerol-treated animals. In addition, histopathological changes induced by glycerol in renal tissue were highly improved in animals given WG.Conclusions: The current findings demonstrate that WG has the ability to attenuate acute kidney injury secondary to rhabdomyolysis induced by glycerol in rats by modulating oxidative stress, as well as inflammatory and rhabdomyolysis markers.