Celecoxib (CLX) is a selective COX-2 inhibitor with anticancer potential in a COX-2 dependent and independent manner. CLX's low water solubility has a dose limiting effect on its utilization in cancer treatment. Here, we developed liposomal drug delivery systems to allow a systemic administration and increase tumor accumulation of CLX based on the enhanced permeability and retention (EPR) mechanism. Nine liposomal formulations has been prepared with different phospholipid compositions; among them three sets of liposomal formulations were selected based on characterization and stability for further studies. Anti-tumor effects of CLX-entrapped liposomal formulations were tested in vitro by cytotoxicity test and in vivo in BALB/c mice bearing C26 colon carcinoma. Biodistribution of liposomal-CLX has been studied by radiolabeling of CLX with I125.The selected formulations had average size of about 100 nm, a narrow monomodal distribution with storage stability of at least one year at 4 °C. The HSPC/DSPG/cholesterol/DSPE-PEG2000/CLX (65/10/10/5/10 molar ratio) liposomal formulation had slowest release profile and greatest antitumor effects in vivo. This liposomal I125CLX formulation had a three times more accumulation in tumor site in comparison to the free I125CLX. Liposomal CLX may serve as a safe, slow release and effective anti-tumor agent and merits further investigation.