In addition to direct killing of tumor cells, PDT can enhance anti-tumor immune responses in the host. It is well known that PDT-induced acute inflammation facilitates PDT-enhanced anti-tumor immunity. Our studies in murine colon carcinoma model demonstrates that PDT induces a short-lived burst of PGE2 in tumor draining lymph node which is critical for ability of PDT to induce acute inflammation. Using a selective COX2 inhibitor NS398, we demonstrate that this short-lived PGE2 burst regulates PDT-enhanced anti-tumor immunity and overall PDT efficacy. These results bring to light a beneficial role of PDT-induced acute expression of PGE2 on PDT-enhanced anti-tumor immunity. Although long term administration of NSAIDS is the current clinical practice for PDT, our research emphasizes on delaying the timing of NSAID administration to after acute inflammation is resolved for optimal response.