In my company, we are using seperately firewall(Pfsense) & Squid Proxy (Centos 5) in a different machine. Users are connected to internet in the following way:

User's PC -> Proxy -> Firewall -> Internet (Wan)

Problem is Outlook not able to communicate with mail server.
Iptables is disabled.

Kindly guide me how to solve this issue. Shall i enable iptables or i need to add rules in proxy & iptables.

where is the mailserver located? which type of proxy and what is it doing>?? you might need to post the config..what is your iptables config ??
disabling the firewall could even be hindering the whole thing....without any sort of configs showing/explanations it would be hard to tell....
many questions you could answer to get the best possible help

Mailserver is located in another location(Different Static IP).
Squid proxy is to block some wesites & Downloads.
No rules are set in iptables. iptable is empty.

ok...more info is needed still.
you say outlook cannot communicate with mailserver.
communicate as in...ping?? traceroute./... telnet to smtp port???
all or some of the above??? where is traceroute failing?? can you tracepath to port 25??? then we can see where it might be failing??

show output from iptables --list

i want to check default policies...
also logs on mailserver...are they picking up access attempts??

more more more info please or at least list some of the troubleshooting methods you have tried so we dont have to keep covering them....