Recent evidence shows that inhaled PM_(2.5) can enter the blood circulatory system and even the brain. However, the damage of blood-borne PM_(2.5) is not clearly elucidated. This work aims to understand and characterize the toxicity, i.e., the acute health effects, of PM_(2.5) that is directly injected into the blood circulatory system. Rats were injected with different dosages (568, the equivalent of 1 year of inhalation for a rat; 93; and 9.3 μg) of PM_(2.5) sampled from Beijing via a sterile catheter injected into the jugular vein. The behaviors of the rats upon external interruptions were recorded. Blood samples were collected before exposure and 1 h, 3 days, 5 days, 7 days, and 9 days after the PM_(2.5) injection for analyzing serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), endotoxin, and 8-hydroxydeoxyguanosine (8-OHdG) levels. After euthanization, the heart, lung, liver, kidney, and spleen were taken and processed for histopathological analysis. PM_(2.5) components were also analyzed. Acute inflammation with 102% and 90% increases for IL-6 and CRP, respectively, was observed 1 h after the 568 μg-PM_(2.5) injection, while oxidative DNA damage occurred only five or more days later, which was accompanied by significantly elevated endotoxin levels. Hemorrhage of lung alveoli and behavioral changes, including fear and non-responsiveness, were also observed. Surprisingly, all exposed rats seemingly survived the PM_(2.5) injection, behaving similarly to the control groups. The immune defense might have played an important role in combating the PM_(2.5) injection. The results showed acute health effects from directly injected PM_(2.5), including rapid inflammation, oxidative damage, and routine-behavioral changes. Further study about the long-term effects of injection and the immune defense is warranted. Nonetheless, the results here suggest that PM_(2.5) health effects may have to some extent been exaggerated in the literature.