Aims PPARγ stimulation improves cardiovascular (CV) risk factors, but without improving overall clinical outcomes. PPARγ agonists interfere with endothelial (EC), monocyte and smooth muscle cell (SMC) activation, function and proliferation, physiological processes critical for arterial collateral growth (arteriogenesis). We therefore assessed the effect of PPARγ stimulation on cerebral adaptive and therapeutic collateral growth. Methods In a rat model of adaptive cerebral arteriogenesis (3‐VO), collateral growth and function were assessed (a) in controls, (b) after PPARγ stimulation (pioglitazone 2.8mg/kg; 10mg/kg compared to metformin 62.2mg/kg or sitagliptin 6.34mg/kg) for 21 days or (c) after adding pioglitazone to G‐CSF (40μg/kg every other day) to induce therapeutic arteriogenesis for 1 week. Pioglitazone effects on endothelial and SMC morphology and proliferation, monocyte activation and migration were studied. Results PPARγ stimulation decreased cerebrovascular collateral growth and recovery of hemodynamic reserve capacity (CVRC controls: 12±7%; pio low: ‐2±9%; pio high: 1±7%; metformin: 9±13%; sitagliptin: 11±12%.), counteracted G‐CSF induced therapeutic arteriogenesis and interfered with EC activation, SMC proliferation, monocyte activation and migration. Conclusion Pharmacologic PPARγ stimulation inhibits proarteriogenic EC activation, monocyte function, SMC proliferation and thus adaptive as well as G‐CSF induced cerebral arteriogenesis. Further studies should evaluate whether this effect may underlie the cardiovascular risk associated with thiazolidinedione use in patients. This article is protected by copyright. All rights reserved.