Chlorin e6 is a stable chlorophyll derivative and can be used in photodynamic therapy (PDT) to treat cancer. One of the synthetic pathways of chlorin e6 is via the transformation of chlorophyll a to methyl pheophorbide a. In this study, we optimize the experimental condition for obtaining methyl phe-ophorbide a from chlorophyll extracted from Spirulina. The preliminary study showed that the suitable solvent system for extracting chlorophyll from the extract was dichloromethane and n-hexane in a ratio of 1:1. To determine the optimal pa-rameters of 4 factors: time, temperature, chlorophyll/H2SO4 ratio (w/v), chlorophyll/MeOH ratio (w/v) to obtain the high-est conversion efficiency of methyl pheophorbide a. The ex-perimental matrix followed the Box-Behnken design to inves-tigate the optimal region, with experiments for four factors at three levels to build the indicator surface. The optimal condi-tions for preparing methyl pheophorbide a from chlorophyll: Chlorophyll/H2SO4 ratio was 4/5 (w/v), chlorophyll/CH3OH ratio was 6/50 (w/v), time was 4.4 hours and temperature was 44oC. Chlorin e6 was successfully prepared from methyl phe-ophorbide a.