Aim: The present study aimed to investigate the effect of meteorological parameters on particulate matter concentration (PM2.5) in ambient air of Karaj metropolitan. Materials and Methods: In this cross-sectional descriptive study, 17 sampling points in Karaj city were chosen using GIS software. Sampling of PM2.5 was carried out for 24 h using the sampling pilot during the four seasons in the air of Karaj city. Sampling of PM2.5 was performed using PTFE filters, peripheral pump, and personal modular impactor. The concentration of particles collected on the filter was calculated by gravimetric method. Meteorological parameters including temperature, humidity, pressure, cloud coverage rate, ultraviolet (UV), and dew point were recorded during sampling through portable devices. Finally, the relationship between PM2.5 concentration and meteorological parameters was assessed by SPSS24 and Excel software. Results: Seasonal variation trends of PM2.5 particles showed that maximum and minimum annual concentrations have happened in autumn and spring seasons with a value of 67.48 and 19.85 μg/m3, respectively. Furthermore, the citizens of Karaj are exposed to PM2.5 pollutants four times more than the Environmental Protection Agency-recommended standard (10 μg/m3). The findings of this study also show that there is a positive correlation between PM2.5 particle concentration and temperature, relative humidity, and pressure (P < 0.05). Moreover, a weak and negative correlation was found between UV radiation, cloud cover, and dew point with PM2.5 particle concentration (P > 0.05). Conclusion: The highest concentrations of particles were observed in autumn season. Furthermore, the particle concentration scatter map shows that the central and eastern regions and north of Karaj are more polluted than other areas. Therefore, to protect the health of citizens of Karaj, appropriate policies and strategies should be adopted to reduce the concentration of particulate matter and other pollutants in the ambient air of this city.