Venlafaxine hydrochloride in situ nasal gel to brain delivery to provide sustained release by improving the residence time of the drug in the nose providing rapid antidepressant effect should improve patient compliance and treatment. The aim of the present study was to develop a venlafaxine hydrochloride (VLF) nasal in situ gel based upon the concept of ion activated gelation of gellan gum for the treatment of depression. The in situ gel was characterized for drug content, gelation, viscosity, gel strength, mucodhesive strength and pH. Formulation F4 showed the effective gelation, viscosity, gel strength along with mucoadhesive strength and non-fickian diffusion process across sheep mucosa. F4 batch released 48.32 ± 2.6 % drug in 4 hours with the flux of 20.15 μg/cm2/hr. Histopathological examinations showed no evidence of mucosal damage. The in situ gel was stable after 3 months stability study. In the pharmacodynamic FST study, the in situ gel treated rats showed significant responses (p<0.001). VLF in situ nasal gel could be potentially safe, effective and improve the residence time of the drug in the nose.