Multifocal posterior pigment epitheliopathy (MPPE) is a rare complication of systemic lupus erythematosus (SLE) and resistant to treatment. We here report a case of SLE with MPPE, successfully treated with prednisolone (PSL) and laser photocoagulation therapy. A 38-year-old woman, who had suffered from SLE for four years, was admitted to our hospital with the complaints of left hemiparesis, right homonymous hemianopsia, and dysarthria. The findings of MRI suggested her symptoms were caused by cerebrovascular involvement of SLE. The treatment with prednisolone was started at a dose of 100 mg per day. While the dose of PSL was reduced, she began to complain of paresthesia in left face and myodesopsia of left eye. Based upon the result of fluorescein angiogram, the diagnosis of MPPE was made. Since MPPE accompanied exacerbation of neurological manifestation, we considered that MPPE was a symptom of vascular involvement of SLE. MPPE was treated with laser photocoagulation therapy and an increased dosage of PSL, with favorable results. It has not been reported, as far as we concern, that laser photocoagulation therapy is effective for MPPE caused by SLE. This case is important for the pathogenesis and therapy of MPPE with SLE.