Malaria still be health problem in the world, especially in Eastern Indonesia. Malaria's inflammation and metabolism defect can cause colonic damage, such as enhancement Muc-1 protein expression and goblet cells hyperplasia. Sambiloto and spirulina combination as antiinflammatory and antioxidative agent can prevent medial colon damage Plasmodium berghei ANKA infected mice. The aim of the study to show the effect of sambiloto and spirulina combination on Muc-1 protein activity in medial colon Plasmodium berghei ANKA infected mice. This study use preserve male Swiss Webser mice colonic tissue which has inoculated by Plasmodium berghei ANKA, whose treatment group include positive control (dehyroartemisin piperaquine), negative control (carboxymethil cellulose), AP (sambiloto), AP+ES (sambiloto+spirulina extract), and AP+PS (sambiloto+spirulina powder) and terminated after 28 days of treatment. Colonic tissue was stained with immunohistochemistry and observed using light microscope (400x) in five different field and was analyzed with ImageJ® sowtware, and statisitcal analysis was done with SPSS 20.0. According to One Way ANOVA and Duncan posthoc test, only AP+PS (120,98 ±3,37), which significantly difference between negative control, AP, and AP+ES group. Meanwhile, between DHP, AP+PS group not significantly differenece. Sambiloto extract and spirulina powder combination can reduce Muc-1 protein expression in medial colon Plasmodium berghei ANKA infected mice.