BACKGROUND: Nicotine can lead to renal damage in hypertension patients. Negative air ions (NAIs) is a natural antioxidant. However, rare research focus on the effect of NAIs on nicotine aggravated oxidative damage and hypertensive kidney damage. METHODS: We used a spontaneously hypertensive rat (SHR) model to investigate the molecular mechanisms for nicotine-exacerbated renal damage and the intervention effect of NAIs. 8-week-old male rats were injected with nicotine or nicotine+ 6 h/d 4.5 × 10 RESULTS: Our results showed that nicotine exacerbated SBP and renal damage, and elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in SHR. After 3 months of 1.5 mg/kg nicotine exposure, serum levels of urea nitrogen (BUN) and transforming growth factor beta 1 (TGF-β CONCLUSIONS: NAIs can attenuated nicotine-exacerbated hypertensive renal damage and fibrosis process through inhibiting oxidative stress and TGF-β/Smad pathway. We suggest that NAIs intervention could be proposed a new approach to adjuvant therapy of chronic kidney disease in smokers with hypertension.