Objective: In the current research study, a colon targeted pulsatile drug delivery system (PDDS) of venlafaxine hydrochloride (VH) was designed for chronotherapy of depression.Method: A capsular device was designed having body insoluble throughout gastrointestinal tract (GIT) fluid and cap soluble in small intestine fluid. The granules of VH was filled in the body and separated from the cap with the help of a hydrophilic polymer plug. Plugs were made up of blend of HPMC K100M and xanthan gum (1:1). Finally, an enteric coating was applied on entire capsule using 5 %w/v ethylcellulose (EC) solution. Results: In in vitro release studies, the enteric coat of the EC was insoluble for 2 h in pH 1.2 (stomach), but get solubilized in pH 7.4 phosphate buffer (small intestine). The cap of the capsule solubilizes in pH 7.4, which exposed the hydrophilic plug to absorb the nearby fluid and swell. After maximum swelling, the plugs got ejected out from the capsule body causing the release of VH granules into colon (pH 6.8 phosphate buffer). Conclusion: Formulations containing high amount of polymer in plug showed 5 h lag time, which was considered optimum for a delivery system to reach colon and release the drug.