Objective: To investigate the regulatory role of IQGAP1 in cytoskeletal rearrangement of podocytes. Methods: Conditionally immortalized mouse podocytes were used to perform cell culture and stimulated by puromycin aminonucleoside (PAN). RT-PCR and Western blot analysis were used to measure the level of IQGAP1 mRNA and protein，respectively. The cytoskeleton of F-actin was evaluated by FITC-conjugated phalloidin staining under laser confocal scanning microscope and semi-quantitative system with cortical-F-actin score (CFS) was used to analyze the degree of actin cytoskeleton arrangement. We further explored the changes of cytoskeletal rearrangement after up- and down-regulation of IQGAP1. Results:①when compared with the control group, the expression of IQGAP1 mRNA and protein was significantly decreased after PAN stimulation in mouse podocytes(P<0.05). PAN stimulation induced cytoskeletal rearrangement including cortical F-actin ring formation, stress fiber attenuation and CFS up-regulation; ②the above rearrangement was exacerbated by IQGAP1 siRNA transfection (P<0.05); ③ PAN induced cortical F-actin ring formation and CFS up-regulation was abated after IQGAP1 plasmid transfection (P<0.05). Conclusion: IQGAP1 can inhibit PAN induced cytoskeleton rearrangement in podocytes and plays an important role in maintaining normal podocyte cytoskeleton.