AIM: To investigate the regulatory roles of the members of the peroxisome proliferator-activated receptor (PPAR) family in lacrimal gland dysfunction under conditions of desiccating stress or diabetes. METHODS: Quantitative polymerase chain reaction (qPCR) was used to examine the expression of PPARs in the cornea, conjunctiva, meibomian gland, and lacrimal gland in adult rats. The rats were divided into 3 groups: a control group, dry eye group, and diabetic group. The phenol red threads test, tear film break-up time (BUT) test and fluorescein staining were carried out to evaluate the development of dry eye. Based on bioinformatics research, qPCR was used to examine the expression level of PPARγ, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), sirtuin 1 (Sirt1), myeloid differentiation factor 88 (MyD88) and transforming growth factor-β (TGF-β) in the lacrimal glands. RESULTS: PPARα and PPARβ/δ were mainly expressed in the conjunctiva and the lacrimal gland, respectively. However, PPARγ was expressed in both the conjunctiva and lacrimal gland, at much higher levels than those measured for PPARα and PPARβ/δ. Dry eye rats and diabetic rats both showed decreased tear secretion, shortened BUT, and increased corneal staining. Significant changes in gene expression were observed compared with the control group. In the lacrimal glands of dry eye rats and diabetic rats, expression of PPARγ decreased (P<0.05), expression of Sirt1 also decreased (P<0.01), whereas expression of TNF-α, IL-1β, IL-6, MyD88, and TGF-β increased (P<0.05). CONCLUSION: Among PPARs, PPARγ might play a dominant role in the regulation of metabolic- and inflammatory-signaling pathways on the ocular surfaces and in lacrimal glands. Down-regulation of PPARγ is highly relevant to lacrimal gland dysfunction under desiccating-stress and diabetic conditions. PPARγ, thus, is a potential therapeutic target in the treatment of environment- or diabetes-induced dry eye diseases.