Microparticles (MPs) are well recognized as a global concern arising from plastic waste. MPs can cause various environmental and health problems. This study was conducted to evaluate the effect of the administrations with MPs for short and long terms on the pathophysiological and histological status of hepatorenal and intestinal tissues in mice. Forty (40) male CD-1 mice were divided into 4 groups (n = 10) as follows; the first group (Gp1) was served as a negative control, administered orally with 200 µl of dist. H₂O. Gp2 was administrated orally daily with MPs (66.4 mg/kg b. wt) for 28 days. Gp3 was administered as in Gp1 for 120 days and used as a negative control for Gp4. Gp4 was administrated with MPs as in Gp2 orally for 120 days. All groups were sacrificed, and blood samples, liver, kidney, and intestinal tissue samples were collected for haematological, biochemical, and histopathological analysis. The results showed that the short-term administration of MPs did not show significant changes on the haematological, biochemical parameters, histological investigations of the hepatorenal and intestinal tissues, however, administration for long term led to significant changes pathophysiological and histopathological alterations in the liver, kidney, and intestinal tissues. In conclusion, administration of MPs for long term could be harmful on the vital organs