Abstract: A series of 2-formyl (acetyl) substituted quinoline thiosemicarbazones(Ⅲ, ⅩⅡ, ⅩⅢ) were prepared in order to evaluate their antimalarial activity. Oxidation of substituted quinolines (Ⅳ) with selenium dioxide gave 2-formyl substituted quinolines(Ⅴ). 2-Acetyl substituted quinoline (Ⅸ) was obtained from Ⅳ by oxidation, esterification, Claisen condensation and decarboxylation. Ⅲ_1～9 were synthesized by two methods; one was by condensation of 2-formyl (acetyl) substituted quinolines with methyl hydrazinecarbodithioat to form methyl - 3- 1-(2, quinolinyl) - alkylidene hydrazinecarbodithioate (ⅩⅠ), then the S-methyl group of ⅩⅠ was displaced by substituted amines to formthe desired substituted thiosemicarbazones. The other was by condensation of 2-formyl (acetyl) substituted quinolines with 4-substituted-3-thiosemicarbazide (Ⅹ) to afford directly Ⅲ_1～9, Ⅲ_10～12 were obtained by selective reduction of corresponding nitro compounds with stannous chloride and ⅩⅡ as a by-product was obtained by the nonselective reduction of Ⅲ₇ with stannous chloride. 3 - Hexyl - 4 - oxothiazolin - 2 - yl (2 - formyl or acetyl substituted quinoline) hydrazones (ⅩⅢ_1,2) were prepared from Ⅲ_1,4 via cyclization under sodium acetate condition. Eighteen compounds were found to be inactive in mice infected with ANKA strain of Plasmodium berghei..