Objectives: Development and evaluation of aripiprazole (AP) loaded lipid based in situ gel system (AP-LIGS) which could maintain the release of drug throughout period circumventing the need of oral therapy. Materials and Methods: AP possesses oral bioavailability (~87%) and biological half-life (~75 h) and undergoes extensive first-pass metabolism. Available AP long term injectable preparations have drawback of simultaneous administration of AP tablets orally for first few weeks, leading to patient non-compliance and making the therapy less effective. AP-LIGS was formulated using phospholipid E80, medium chain triglyceride and ethanol. Optimization was done by evaluating the effect of water content on viscosity of prepared AP-LIGS and % cumulative drug release (% CDR) at day 1. Results: Optimized AP-LIGS showed rapid gelation with minimum lag time and in vitro drug release profile upto 6 weeks. In vivo depot formation was confirmed by gamma scintigraphy after subcutaneous injection of liquid state of AP-LIGS. Histopathological study revealed its safety and biocompatibility with surrounding tissues since no alteration or any inflammation was observed at the injection site even after 45 days of subcutaneous administration. In vivo neurobehavioral assessment was done for assessing the efficacy of AP-LIGS system using Morris water Maze (MWM) test. MK-801 (Dizocilpine) model was used for inducing schizophrenia in Sprague-Dawley rats. All three parameters escape latency, time spent in target quadrant and total distance travelled was significantly improved (p <0.001) in AP-LIGS group when compared to MK-801 group at all time points. Conclusion: Developed novel AP-LIGS system is safe and may be used as a promising approach for sustained drug release and effectively manage schizophrenia.