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Introduction Perivascular adipose tissue (PVAT) is an adipose tissue depot that modulates vascular tone and exerts an ‘anti-contractile’ effect in health which is lost in obesity. Phenanthrene (Phe) is a common air pollutant that is associated with cardiometabolic disease. Phe has previously been reported to alter adipokine release from adipose tissue, but the effects of Phe on PVAT function and vascular contractility have not been investigated.Methods and Results Isometric contraction of isolated mesenteric resistance arteries ±PVAT (≤200µm diameter) from C57Bl/6J mice was measured using wire myography. Arteries were exposed to 20µM Phe for 15 minutes prior to stimulation with noradrenaline (NA; 1nM – 30µM). Acute Phe exposure significantly reduced the contractility of -PVAT vessels from male and female mice (n=8 both sexes, P<0.0001) and significantly increased the contraction of +PVAT arteries from both sexes at the highest concentration of NA only (P<0.05).The effects of in vivo Phe exposure were investigated by exposing 8-week-old mice to 6µg/kg bw/d in drinking water for 10 weeks; some animals were fed an obesogenic 60% kcal from fat diet (HFD) alongside Phe exposure (n=4-5 per group). Obese female animals had impaired glucose tolerance (lean control vs obese control, P<0.001; lean Phe vs obese Phe, P<0.01) and the blood pressure of obese vehicle exposed female animals was elevated, compared to lean vehicle animals (systolic, P<0.05; diastolic, P<0.01). Using wire myography, in contrast to the acute in vitro exposure experiments -PVAT arteries from lean male mice chronically exposed to Phe contracted more compared to control (P<0.001), whereas -PVAT arteries from obese males exposed to Phe contracted significantly less (P<0.05) like the acute in vitro exposure experiments. There was no effect of chronic Phe exposure on the contractility of ±PVAT arteries from lean females or on +PVAT arteries from lean or obese male mice. In obese females however, similar to obese males and the in vitro exposure experiments, chronic Phe treatment significantly decreased the contractility of -PVAT arteries (P<0.0001), while increasing the contractility of +PVAT arteries (P<0.05). Overall, the PVAT anticontractile effect was lost in obese female animals exposed to Phe but not vehicle exposed mice.Conclusion In vitro acute incubation with Phe reduced the contractility of -PVAT arteries from both sexes. The vascular effects of chronic in vivo exposure to Phe differed between diets, exposures and sexes. Interestingly, lean females were protected from the effects of Phe exposure while Phe exposure in obese females resulted in the loss of the PVAT anticontractile effect. These results suggest that in health PVAT may play a protective role in the air pollution induced vascular dysfunction. More investigation is required to understand the mechanism by which Phe affects vascular contractility and the role that PVAT may play.