The present invention discloses a porphyrin derivative with large substituent and its pharmaceutical acceptable salt and its preparation method. The described porphyrin derivative is M-5,10,15,20-tetra[(N)-substituted-n-phenyl or heterocyclic radical] porphyrin, in which n represents 2,3 and 4 postion substitution, and M is one of Fe, Mn, Co, Ni, Cu Zn, Sn, Cr and V metal ions. Said invented porphyrin derivative has higher steric hindrance, and can effectively resist the combination of porphyrin with DNA, and can reduce the mutual transformation between the different isomers, reduce toxicity of porphyrin and raise its medicinal practicability. The described porphyrin derivative can be used as small molecular antioxidant for regulating concentration of peroxide between cells of human body or in cell.