Methylprednisolone pulse therapy (MPT) was introduced to avoid life-threatening complications in patients with systemic lupus erythematosus (SLE) with brain manifestations; however, the efficacy of MPT in SLE patients with brain involvement is still uncertain and needs to be objectively evaluated. We enrolled 15 female SLE patients with neuropsychiatric manifestations in this study. All patients had normal brain MRI and abnormal brain HMPAO-SPECT findings. Follow-up HMPAO-SPECT studies were conducted 2 weeks after MPT. Serum levels of anticardiolipin antibodies (ACA) and anti-ribosomal P antibodies (anti-P) were measured before and after MPT. Before MPT, 7 patients were positive for ACA and 7 patients were positive for anti-P. After MPT, none of the 15 patients demonstrated positive serologic findings or neuropsychiatric manifestations. Based on the follow up brain HMPAO-SPECT images following MPT, 13 patients showed disappearance of the perfusion defects and 2 patients showed partial recovery of rCBF. Brain HMPAO-SPECT imaging is a logical and objective tool for measuring the effects of MPT in SLE patients with brain involvement by determining of changes in rCBF.