Nerve growth factor (NGF) has been shown to protect the viability of kidney cells in acute phase of renal damage. However, since the half-life of NGF is very short, it is too large to pass the blood-brain barrier and rapidly transported to the liver for catabolizing its use in therapy is limited. 4-Methylcatechol (4MC) is a substance that increases NGF synthesis in many tissues. This study aimed to investigate the protective effects of 4MC against acute renal injury induced by streptozotocin (STZ). We have investigated the profibrotic, proinflammatory, oxidative changes in STZ-induced acute renal damage and the possible role of the NGF/TrkA system and Akt/GSK3β/β-catenin pathway in this mechanism. Experiment was designed as to be started with injection of 4MC for 10 days as a single dose (10 μg/kg) per day and to be terminated after 4 h of a single dose (75 mg/kg) STZ injection. As the result, 4MC pre-treatment decreased kidney damage, ROS production, the renal levels of TGFβ1, CD68, tumor necrosis factor-α and interleukin 1β. Moreover, 4MC pre-treatment increased levels of NGF and its receptor TrkA, p-Akt (Thr308), p-GSK3β (Ser9) and nuclear β-catenin. These data suggest that 4MC prevents the development of STZ-induced renal damage by suppressing ROS production and inflammation via Akt/GSK3β/β-catenin pathway which may be stimulated by NGF/TrkA signaling. Therefore, 4MC can be suggested as a potential agent for the prevention of acute renal injury.