Photodynamic therapy (PDT) had been shown effective in the treatment of intimal hyperplasia, which contributes to restenosis, by eradicating cells in the vessel wall. This study is designed to evaluate the effects of PDT with protoporphyrin IX (PpIX) on the viability of vascular smooth muscle cells (SMCs) and to define the cell-death pathway Fluorescence microscopy and laser-induced fluorescence spectroscopic detection showed that SMCs selectively uptake PpIX, and the intracellular PpIX concentration increases with the amount of PpIX in the incubation solution PDT with PpIX impaired cellular viability from 93 +/- 3.4% to 36 +/- 3.9% when the light intensity increases from 2 to 9 J/cm(2) and intracellular PpIX concentration increases from 0.5 to 20 mu g/ml. Although PDT induced both apoptosis and neciosis, the ratio of apoptotic cells increased with light dosage or intracellular PpIX concentration The loss of mitochondial membrane potential coincided with the apoptotic ratio Our results Indicated that the induction of apoptosis of SMCs may be one of the mechanisms by which PDT inhibits restenosis in vivo (C) 2009 Elsevier Inc All rights reserved.