Aim To investigate the effects of OPN-002-siRNA transfection on intimal hyperplasia and osteopontin （OPN）, transforming growth factor-β1 （TGF-β1）, proliferating cell nuclear antigen （PCNA） expression after carotid balloon injury in rat.Methods Through preliminary experiment, OPN mRNA in cultured vascular smooth muscle cells was tested by real-time reverse transcription polymerase chain reaction （real-time RT-PCR）, and OPN-002-siRNA was determined as the most sensitive sequence and used as transfected siRNA in the subsequent animal experiments. Seventy-two rats were randomly divided into four groups: sham group, balloon injury group, OPN-scramble-siRNA （OPN-SCR-siRNA） group and OPN-002-siRNA group. Changes of intimal hyperplasia and OPN, TGF-β1, PCNA expressions were detected by immunofluorescence, hematoxylin-eosin （HE） staining, real-time RT-PCR and Western blot, and also the effect of OPN-002-siRNA was studied on them.Results （1）There was no apparent neointima on the 3rd day after balloon injury. Intima began to thicken on the 7th day after injury, and intimal thickening was significant on the 14th day. （2）The expression of OPN, TGF-β1 mRNA and protein started to increase on the 3rd day and persisted until the 14th day. The expression of PCNA mRNA and protein started to increase on the 3rd day, peaked on the 7th day, decreased on the 14th day. （3）Compared with balloon injury group and OPN-SCR-siRNA group, the neointima thickness decreased significantly on each time point in OPN-002-siRNA group （P<0.001）, and both mRNA and protein expression of OPN, TGF-β1 and PCNA reduced significantly on each time point in OPN-002-siRNA group （P<0.001）.Conclusion OPN-002-siRNA can inhibit intima hyperplasia after artery injury by decreasing the expression of OPN, TGF-β1 and PCNA.