Rosacea is treated among others by doxycycline and sodium bituminosulfonate dry substance (SBDS). We addressed the molecular mechanism(s) underlying the therapeutic benefit of SBDS and doxycycline. Therefore, we investigated whether SBDS or doxycycline regulates the expression of signal molecules relevant for inflammatory and angiogenic effects. Cyclooxygenase 1 (COX1) and COX2 activity assays were assessed in primary human monocytes. The release of nitric oxide (NO) and their synthesizing enzyme inducible nitric oxide synthase (iNOS), VEGF and LL37 release were determined in lung epithelial cells A549, mast cells HMC 1.2 or in normal human epidermal keratinocytes (NHEKs), respectively. The IC(50) values of SBDS for the inhibition of recombinant human COX-1 and COX-2 were 1.9 and 8.3 µg/ml, respectively. In an inflammatory state (COX-2 expression) 100 µg/ml SBDS reduced PGE(2) and TXB(2) release in primary human monocytes. 25 µg/ml SBDS inhibited the mRNA and protein expression of iNOS. Moreover, 50 µg/ml SBDS and 30 µg/ml doxycycline inhibited the release of VEGF in an inflammatory state in HMC 1.2 cells. Both drugs did not affect LL37 release. Doxycycline did not affect intracellular NO levels and iNOS expression. SBDS and doxycycline mediate anti-inflammatory and anti-angiogenic effects through similar but also different signaling molecules.