Early diagnosis of and subsequent monitoring of therapy for rheumatoid arthritis (RA) could benefit from detection of (sub)clinical synovitis. Imaging of (sub)clinical arthritis by targeting the translocator protein (TSPO) on activated macrophages is feasible using (R)-[¹¹C] PK11195-based positron emission tomography (PET), but clinical applications are limited by background uptake in peri-articular bone/bone marrow. The purpose of the present study was to evaluate two other TSPO ligands with potentially lower background uptake in neurological studies, [¹¹C]DPA-713 and [¹⁸F]DPA-714, in a rat model of arthritis. TSPO binding of DPA-713, DPA-714 and PK11195 were assessed by in vitro competition studies with [³H]DPA-713 using human macrophage THP-1 cells and CD14⁺ monocytes from healthy volunteers. In vivo studies were performed in rats with methylated bovine serum albumin-induced knee arthritis. Immunohistochemistry with anti-TSPO antibody was performed on paraffin-embedded sections. Rats were imaged with [¹¹C]DPA-713 or [¹⁸F]DPA-714 PET, followed by ex vivo tissue distribution studies. Results were compared with those obtained with the tracer (R)-[¹¹C]PK11195, the established ligand for TSPO. In THP-1 cells, relative TSPO binding of DPA-713 and DPA-714 were 7-fold and 25-fold higher, respectively, than in PK11195. Comparable results were observed in CD14⁺ monocytes from healthy volunteers. In the arthritis rat model, immunohistochemistry confirmed the presence of TSPO-positive inflammatory cells in the arthritic knee. PET images showed that uptake of [¹¹C]DPA-713 and [¹⁸F]DPA-714 in arthritic knees was significantly increased compared with contralateral knees and knees of normal rats. Uptake in arthritic knees could be largely blocked by an excess of PK11195. [¹¹C]DPA-713 and [¹⁸F]DPA-714 provided improved contrast compared with (R)-[¹¹C]PK11195, as was shown by significantly higher arthritic knee-to-bone ratios of [¹¹C]DPA-713 (1.60 ± 0.31) and [¹⁸F]DPA-714 (1.55 ± 0.10) compared with (R)-[¹¹C]PK11195 (1.14 ± 0.19). [¹¹C]DPA-713 and [¹⁸F]DPA-714 clearly visualized arthritis and exhibited lower (peri-articular) bone/bone marrow uptake than (R)-[¹¹C]PK11195. These features merit further investigation of these tracers for early diagnosis and therapy monitoring of RA in a clinical setting.