The unique ability of chlorophyll derivatives to accumulate in tumor tissues and cause a photodynamic effect under laser radiation has been successfully used in photodynamic therapy (PDT). Previous research on modified peripheral substituents in chlorophyll showed that the presence and position of substituents in chlorin derivatives remarkably affect biological activities. Herein, we synthesized methyl pyropheophorbide-a (MPPa) derivatives, which are chlorophyll-a derivatives with heterocyclic aromatic substituents or pyrazole moieties on the peripheral positions. Then, we examined the PDT effects of these new derivatives in vitro and in vivo.