Introduction: Stress is an important factor of depression that causes the changes in various body systems. Animal health including human has been shown to be affected by the stressful events of life inducing situation which alters cognition, learning, memory and emotional responses, causing mental disorders like depression and anxiety. Aim & Objectives: The study was undertaken to assess the various neurobehavioral changes in mice applying restraint stress in mice after exposure to restraint stress. Methods: The experiment was carried out with 12 healthy male mice weighing about 25-35gms. The animals were randomly divided into two groups of six animals each. Group I-control and Group II - restraint stress group. The restraint stress group mice were placed in specially constructed restraint meshes for 6 hours (between 10.00 am - 04.00 pm) for 21 days. The neurobehavioral assessment were done after 21 days by using open field apparatus and elevated plus maze for evaluating locomotor activity, emotional and anxiety status in mice. Results: After 21 days of restraint stress, there was a significant (P<0.001) decrease in ambulation, rearing and grooming, whereas the immobilization time was significantly (P<0.001) increased when compared with their normal controls. In elevated plus maze, time spent in open arm, number of entries in open arms and number of entries in closed arms was significantly (P<0.01) decreased when compared to control group. Conclusion: Restraint stress produces an inescapable physical and mental stress to which adaptation is seldom exhibited but in