Abstract:[Background] Enteritis is one of the clinical signs of pigs infected with porcine circovirus type 2 (PCV2), and it has an impact on pig performance. It can lead to reproductive failure. The cecum is an essential digestive organ in monogastric animals, and the impact of PCV2 infection on it should be investigated. [Objective] The purpose of this study was to look into the immunological activity and flora of the cecum after PCV2 infection. [Methods] Twelve healthy weaned piglets were randomly assigned to the control (n=6) or infection (n=6) groups. Piglets in the infection group received the virus via oral delivery (5 mL) and intramuscular injection (5 mL), for a total of 10 mL/piglet. The control group was similarly injected with PK15 cell culture. The viral nucleic acid load and antibody dynamics were identified 56 days post-infection (dpi), and micromorphology, viral antigen distribution, immune function, and microbial ecology in pig cecum contents were also examined at 21 and 56 dpi. [Results] PCV2 antigen signal was greater at 21 dpi than at 56 dpi, and viral nucleic acid load and antibody in serum were both at high levels. PCV2 antigen was mostly dispersed in the epithelial cells and lamina propria of the cecum mucosa. While the ability of T cells to proliferate was greatly increased, the amount of SIgA in cecal secretions was significantly reduced. Pigs with the infection experienced significant cecal epithelial cell loss and intestinal gland atrophy. Diversity and quantity of the cisternal vegetation were greatly diminished. Beneficial bacteria like Butyrivibrio and Ruminococcaceae-NK4A214-group were noticeably reduced, whereas conditional harmful bacteria like Alloprevotella were noticeably elevated. The viral nucleic acid load decreased to 7 dpi at 56 dpi, whereas the antibody level remained high. Other indicators essentially reverted to control group levels. [Conclusion] PCV2 infection causes immune dysfunction in the piglets’ cecum, which damages the cecum mucosa and results in an increase in conditionally pathogenic bacteria and a decrease in beneficial bacteria. These changes are connected to the viral content.