Ulcerative colitis (UC) is a part of incurable chronic inflammatory disease that has gained importance over the past few decades. A lot of research has been done to find effective treatments for UC, one of which is herbal medicine. Phaleria macrocarpa (PM), an Indonesian native plant, is thought to be an alternative therapy for UC because of its anti-inflammatory properties. Therefore, in this research, Phaleria macrocarpa Leaves Ethanol Extract (PMLEE) is used to assess its effect on UC by using Caspase-3 as apoptosis marker. PMLEE was made from dried material of PM that undergo maceration. Animals were separated into six groups: normal, negative control, positive control, and PMLEE groups (100, 200, 300 mg/kgBW). PMLEE was then injected to BALB/c mice that have been induced by dextran sodium sulphate (DSS) for 7 consecutive days. DSS is used to model UC in mice colon tissue. All animals were sacrificed and their colons were collected then stained with anti-Caspase-3. The stained sections were subsequently examined with ImageJ based on color intensity which generated H-Score as the results. Based on H-Score of each group, PMLEE 300mg has significantly upregulate the expression of Caspase-3 compare to the negative control (p=0.015). PMLEE also has a tendency to be dose dependent based on the significant difference between PMLEE doses. Therefore, it concludes that PMLEE is able to upregulate the expression of Caspase-3 in colon cells as in this study it was directly proportional.