<p style="text-align: justify;"><strong>Objectives:</strong> Development and evaluation of aripiprazole (AP) loaded lipid based<em> in situ </em>gel system (AP-LIGS) which could maintain the release of drug throughout period circumventing the need of oral therapy. <strong>Materials and Methods: </strong>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. <strong>Results: </strong>Optimized AP-LIGS showed rapid gelation with minimum lag time and <em>in vitro</em> drug release profile upto 6 weeks. <em>In vivo </em>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. <em>In vivo </em>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 (<em>p </em><0.001) in AP-LIGS group when compared to MK-801 group at all time points. <strong>Conclusion: </strong>Developed novel AP-LIGS system is safe and may be used as a promising approach for sustained drug release and effectively manage schizophrenia. <p style="text-align: justify;"><strong>Key words: </strong> Aripiprazole, Gamma scintigraphy, Injectable, In-situ gel, Phospholipid E80, Schizophrenia.