Simple SummaryPorcine reproductive and respiratory syndrome virus (PRRSV) infection causes massive financial losses in pig production worldwide. Vaccination is still the most cost-effective tool to handle PRRSV infection. PRRSV induces apoptosis in different organs. Angiotensin II (Ang II) participates in the inflammatory response, cell proliferation, migration, and apoptosis. The objective of the current study was to assess the concentration of Ang II in the serum of piglets following immunization against PRRSV through intradermal (ID) or intramuscular (IM) vaccination with a commercial PRRS modified live virus (MLV) vaccine. The results indicated differences in viremia of tested piglets at 7 weeks of age, while piglets at 10 weeks of age were all found qRT-PCR positive for PRRSV. Moreover, significant differences were noticed in Ang II in 7-week-old piglets. In conclusion, our study provides evidence that ID vaccination induces less tissue damage, based on the lower measurements of Ang II in the serum of ID vaccinated piglets.The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces apoptosis in different organs. Angiotensin II (Ang II) is the main effector of the renin-angiotensin system and participates in apoptosis. Thus, this study aimed to investigate changes in piglet serum Ang II levels following intradermal (ID) and intramuscular (IM) vaccination with a commercial PRRS modified live virus (MLV) vaccine. The trial was conducted in a commercial pig farm, including 104 piglets which were randomly allocated to four groups: Group A—Porcilis PRRS ID, Group B—Porcilis PRRS IM, Group C—Diluvac ID and Group D—Diluvac IM. The study piglets were either vaccinated or injected at 2 weeks of age and they were tested by qRT-PCR for PRRSV and by ELISA for Ang II. The results indicated differences in viremia of tested piglets at 7 weeks of age, while piglets at 10 weeks of age were all found qRT-PCR positive for PRRSV. In addition, significant differences were noticed in Ang II in 7-week-old piglets. In conclusion, the present study provides evidence that ID vaccination induces less tissue damage, based on the lower measurements of Ang II in the serum of ID vaccinated piglets.