Due to the opportunistic nature of Herpes simplex viral infections, it is of great public concern in subSaharan Africa. To date, there is no vaccine or cure for this viral infection. In this study, anti-viral activity of the Kenyan Chrysanthemum cinerariaefolium (Pyrethrum) against Herpes simplex virus (HSV-1) was evaluated in vivo (using Swiss mice). Phytochemical screening for presence of secondary metabolites of both methanol and aqueous extract of the plant material (flowers) indicated positive, for presence of alkaloids, flavonoids, phenols, saponins, tannins and terpenoids. The extracts were given orally after acute oral toxicity results (LD50 ˃2000 mg/kg of body weight) indicated both extracts are safe to be given orally. Upon induction of topical infection with HSV-1 virus, 2 dose levels (10 mg/kg and 25 mg/kg of methanol extract and 25 mg/kg and 50 mg/kg of aqueous extract) of both extracts were administered, 2 times per day for 7 successive days. Results showed Acyclovir (ACV) at 5 mg/kg and organic extract at 10 mg/kg delayed onset of lesion in local regions significantly (Ƿ ≤ 0.05 test vs. control by student t test). Also, both the organic extract (at a concentration of 10 mg/kg and 25 mg/kg) and aqueous extract (at a concentration of 50 mg/kg) delayed progression of infection significant (Ƿ ≤ 0.05 test vs. control by repeated measures ANOVA). The results indicate extracts from C. cinerariaefolium are active against Hsv-1. So, further investigation is recommended in the Kenya grown C. cinerariaefolium, on its bio-active compounds, safety, and activity on other members of the family Herpesviridae.