Long noncoding RNA (lncRNA) and factors influencing lncRNA expression are related to the nervous system diseases. The aims of the project are to study the effect of lncRNA uc.48+ siRNA on calcitonin gene related peptide (CGRP) release in the spinal cords (SCs) of diabetic neuropathic pain (DNP) rats to identify its possible mechanism and to provide new experimental evidence for the prevention and treatment of DNP. Male Sprague-Dawley rats were used to create a DNP rat model by feeding the rats a high-fat and fructose diet in addition to an intraperitoneal injection of streptozocin. Fasting blood glucose (FBG), mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured to select the DNP rats. The DNP rats were randomly divided into the following 4 groups: (1) a normal control group (Control), (2) a DNP rats treated with saline group (DNP), (3) a DNP rats treated with uc.48+ siRNA group (DNP + uc.48+ siRNA) and (4) a DNP rats treated with scrambled siRNA group (DNP + scramble siRNA). After intrathecal injection of uc.48+ small interfering RNA, the MWT and TWL of the DNP group significantly decreased compared to the Control group, but after the injection of uc.48+ small interfering RNA, the MWT and TWL of the DNP rats significantly increased (P<0.01, ANOVA test). The application of the methods of qPCR and WB produced results that revealed that the expressions of lncRNA uc.48+, CGRP, IL-1β and TNF-α in the SCs of the DNP group were much higher than those in the Control group (P<0.01, ANOVA test), but the expressions of these molecules in the DNP + uc.48+ siRNA group significantly decreased compared with the DNP group (P<0.01, ANOVA test). The phosphorylations of p38 and ERK1/2 in the DNP group were significantly enhanced compared with the Control group, whereas uc.48+ siRNA significantly reduced the increased phosphorylations of p38 and ERK1/2 pathway in the SCs of the DNP rats (P<0.01, ANOVA test). ELISA results revealed that uc.48+ siRNA significantly decreased the high levels of IL-1β and TNF-α in the sera of the DNP rats (P<0.01, ANOVA test). Therefore, lncRNA uc.48+ may play an important role in the transmission of DNP by promoting the release of CGRP in the SC. Small interfering lncRNA uc.48+ might alleviate the hyperalgesia and allodynia of DNP rats by suppressing the release of CGRP in the SCs of DNP rats, which might inhibit the phosphorylations of p38 and ERK1/2 and suppress the release of IL-1β and TNF-α in the SCs of DNP rats.