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Despite strong efforts and promising results in this field, PDT has not yet been approved by any regulatory authority for the treatment of colorectal cancer, one of the most prevalent gastrointestinal tumors. In the search of novel therapeutic strategies, we examined the <jats:italic>in vivo<\/jats:italic> effect of PDT with a lipophilic phthalocyanine (Pc9) encapsulated into polymeric poloxamine micelles (T1107) in a murine colon carcinoma model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design\/Materials and Methods<\/jats:title><jats:p>In vivo assays were performed with BALB\/c mice challenged with CT26 cells. Pc9 tumor uptake was evaluated with an <jats:italic>in vivo<\/jats:italic> imaging system. Immunofluorescence, western blot, and flow cytometry assays were carried out to characterize the activation of apoptosis and an antitumor immune response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pc9\u2010T1107 effectively delayed tumor growth and prolonged mice survival, without generating systemic or tissue\u2010specific toxicity. The induction of an apoptotic response was characterized by a decrease in the expression levels of Bcl\u2010X<jats:sub>L<\/jats:sub>, Bcl\u20102, procaspase 3, full length Bid, a significant increment in the amount of active caspase\u20103 and the detection of PARP\u20101 cleavage. Infiltration of CD8<jats:sup>+<\/jats:sup> CD107a<jats:sup>+<\/jats:sup> T cells and higher levels of interferon\u2010\u03b3 and tumor necrosis factor\u2010\u03b1 were also found in PDT\u2010treated tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pc9\u2010T1107 PDT treatment reduced tumor growth, inducing an apoptotic cell death and activating an immune response. Lasers Surg. 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