Demodex mites are normal residents of the pilosebaceous follicles of healthy human facial skin, at low density, without inducing inflammatory response by skin resident cells (SRCs). When the Demodex population increases, such as in rosacea, an inflammatory response is initiated. The aim of this study is to evaluate how Demodex mites modulate inflammation in SRCs. Skin biopsies from rosacea patients were assessed histologically. Hair follicles were dilated or ruptured, contained mites and occasional inflammatory cells. There was mixed perifollicular inflammation and occasionally mite remnants were found within perifollicular granulomas. Live mites, isolated from human skin surface biopsies, were co-cultured with keratinocytes (HaCaT) or sebocytes (SZ95) for 24 hours at low (1 mite/cm2) and high (5 mites/cm2) densities representing normal and pathologic conditions respectively. Gene expression was analysed by RT-PCR and protein expression by flow cytometry or ELISA. A low density of mites did not induce the release of inflammatory mediators in HaCaT. However, a high density significantly increased the release of TNFα (p<0.01) IL-8 (p<0.05), and CCL2 (p<0.05) in both keratinocytes (n=8) and sebocytes (n=5). Demodex induced TLR2 gene and protein expression (p<0.01) and KLK5 release (p<0.05) only in keratinocytes whereas IL-6 was only released by sebocytes (p<0.05). Our results show that Demodex mites modulate inflammatory responses from SRCs depending on their density. Moreover, keratinocytes and sebocytes respond differently to Demodex stimulus. The contrasting effects on inflammatory responses provide evidence that they co-exist with host cells under normal skin conditions without disrupting the biobalance and have the capacity to induce inflammation when their population is markedly increased as frequently occurs in rosacea.