Obesity is associated with chronic low-grade systemic inflammation. Bariatric surgery has been shown to reduce this inflammation. Here, the effect of a nonsurgical bariatric technique, the duodenal-jejunal bypass liner (DJBL), on systemic inflammation was investigated. Seventeen obese patients with type 2 diabetes were treated with the DJBL for 6 months. Plasma C-reactive protein (CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were determined prior to and during DJBL treatment. Three months after initiation of DJBL treatment, TNF-α levels had increased from 1.8 ± 0.1 to 2.1 ± 0.1 pg/mL, whereas IL-6 increased from 2.7 ± 0.3 to 4.0 ± 0.5 pg/mL (both p < 0.05). CRP and MPO also increased, though the differences were not significant. After 6 months, the levels of all parameters were similar to baseline levels (CRP, 4.2 ± 0.6 mg/L; TNF-α, 2.0 ± 0.1 pg/mL; IL-6, 3.5 ± 0.5 pg/mL; MPO, 53.6 ± ng/mL; all p = ns compared to baseline). In the current study, 6 months of endoscopic DJBL treatment did not lead to decreased systemic inflammation.