Cutaneous leishmaniasis (CL), a dermatological parasitic infection caused by Leishmania major and L .tropica. This disease is still one of the health problems in the tropical and sub tropical parts of world, region and Iran. Although, artemisinin (qinghaosu) is widely used as anti-malarial agent, it is also demonstrated its anti-promastigote effects on some leishmania species. Inflammatory responses against leishmania consist of chemokines, immune cells and mediators. This study investigates two immunological pathways including nitric oxide (NO) and C-reactive protein (CRP) in L. major infected Balb/c mice following treatment with artemisinin and glucantim. Plasma was investigated for NO and CRP alterations using Griess Micro Assay (GMA) and Latex S. Nemati, H. Nahrevanian, A. Haniloo and M. Farahmand Agglutinations Test (LAT) respectively. The results indicated a significant decline in NO levels due to atemisinin treatment (P≤0.05) and in untreated group (P≤0.05). No changes in CRP were observed in experimental groups. It is indicated that L. major infection naturally decreased NO induction in Balb/c mice as a result of amastigote action; therefore artemisinin was not able to increase NO to combat parasite. It is concluded that artemisinin/glucantim action in CL was not associated with NO and CRP pathways; however more studies are needed to clarify other immunological parameters.