While the effects of chronic exposure to microplastic particles (MPs) are extensively studied, the outcomes of a single treatment have received relatively less attention. To investigate MPs’ potential acute toxicity, including their impact on general health status (victual consumption, sensorimotor deficits, and clinical toxicity signs) and serum biochemical parameters (markers of organ/tissue function and oxidative stress indicators), we administered thoroughly characterized MPs (1.4, 35, or 125 mg/kg), generated from polyethylene terephthalate (PET) bottles, to adult male Wistar rats via oral gavage. The MPs’ short-term effects were assessed with well-established tests and methods. The results point to the absence of sensorimotor deficits and clinical toxicity signs, while levels of markers of liver, heart, and kidney function were altered in all MP groups. Decreased victual consumption and increased levels of oxidative stress indicators were evident following treatment with the two higher MP doses. Presented data indicate that examined MPs are able to initiate the development of local changes in tissues and organs within a short time frame, potentially leading to their damage and dysfunction. This study may increase the awareness of the detrimental effects of plastic contamination, as even a single exposure to MPs may provoke adverse health outcomes.