Adverse cardiovascular and inflammatory outcomes after airborne particulate matter (PM) inhalation have long been a topic of epidemiological studies. Previous studies have identified, the microcirculation as particularly vulnerable to this insult. However, the mechanisms of microvascular dysfunction are complex and vary with each specific aerosol. Variations in neurohormonal and inflammatory status contribute to the complexity of defining mechanisms of microvascular dysfunction caused by aerosols. Given the recent identification and toxicological concerns surrounding micro‐ and nanoplastic exposures, we aimed to evaluate microvascular reactivity after acute plastic particle inhalation in this study. Virgin female Sprague Dawley rats in estrus were exposed to filtered air or aerosolized polyamide (i.e., nylon) particles in a whole‐body inhalation chamber. We hypothesized the uterine microvascular reactivity would achieve a vasoconstrictive state due to plastic particle inhalation. Exposure only during estrus served to control for neurohormonal differences within groups. 24h later, the radial arteriole of the uterus was selected as a representative vessel for the microcirculation. Ex vivouterine radial arteriole reactivity was assessed using pressure myography Living Systems Instrumentation, St. Albans, VT). Vascular reactivity was assessed based on responses to endothelium‐dependent (methacholine, MCh, 10‐9‐10‐4 M), –independent (sodium nitroprusside, SNP, 10‐9‐10‐4 M), and smooth muscle contractility (phenylephrine, PE, 10‐9‐10‐4 M). Inflammatory cytokines (IL‐4, IL‐6, MCP‐1, CXCL1; Sigma, St. Louis, MO and IL 5; Abcam, Cambridge, UK) were quantified in plasma with ELISA. Acute inhalation exposure to polyamide MNPs led to significantly impaired vascular reactivity through endothelium‐dependent and vascular smooth muscle mechanisms. Percent maximum dilation in response to 10‐9 M MCh was significantly reduced in exposed animals when compared to controls (‐9.44% ± 3.65 vs. 7.26% ± 4.61). Smooth muscle contraction was also impaired with percent maximum dilation in response to 10‐8 M PE being significantly increased in exposed animals compared to controls (‐9.56%±7.28 vs. ‐59.7±17.4). The levels of IL‐6 were not significant between groups which suggests systemic inflammation may not be a key component of plastic aerosol induced vascular dysfunction. In summary, exposure to polyamide MNPs resulted in less vascular reactivity to pharmacologic stimuli during estrus. However, the mechanisms attributing to disrupted microvascular function remain elusive. An important consideration for future studies will be the proper time point in which various cytokines can be assessed and the reproductive ramifications of these findings. Future studies should examine the impact of plastic particulate inhalation on endothelial inflammatory activation, metabolism, or apoptotic mechanisms. Altogether this information may give insight into how plastic particle inhalation could impair distal tissue health, including endometrial perfusion and ability to sustain pregnancy.