Tremendous improvements have been achieved in growth rates and feed efficiency in commercial broiler birds. However, fast growth broilers generally show weak immune competence and disease resistance. Innate immunity is the first line of defense providing immediate killing effects to a broad range of infectious pathogens and limiting infections to a minimum at an early stage before the activation of more specific adaptive immunity. Acute phase proteins (APPs), defensins and Toll-like receptors (TLRs) are all important innate immune molecules functioning from recognition to killing the foreign microbes. Tibial dyschondroplasia (TD) is one chicken disease associated with rapid growth in broilers. The objective of this research was to study the differential expression of innate immune related genes in liver and spleen tissues between commercial broilers and layers with the stimulation of lipopolysaccharide (LPS). Also, this study investigated mechanisms involved in the pathogenesis of TD at molecular levels. This study first identified and annotated nineteen new chicken APPs genes from the chicken genome draft with bioinformatics tools. Using a relative quantitative real-time RT-PCR method, the expression levels of all thirty-one APPs, thirteen defensins and eight TLRs genes were systemically investigated at the transcriptional level at three time points (0-, 3-, 8-hour) with the challenge of LPS. This study showed that broiler birds generally expressed significantly lower levels of all three families of innate immune related genes than layers and the inductive extent of these genes are generally smaller in broilers too. Close investigation of some important signaling transcription factors (NF-kB and IRF-3) and cytokine (IL-6) also reached the same conclusion. This study revealed that the inadequate expression of deiodinase type 2 (DIO2) contributed to the pathogenesis of TD in rapid growth broilers. All of the experimental results solidly validate the hypothesis that a compromised innate immune response or weak disease resistence is associated with fast growth broiler birds.